tbuckley/cabot-search huggingface dataset:
Racial and Ethnic Differences in the Association of Low-Carbohydrate Diet With Mortality in the Multi-Ethnic Study of Atherosclerosis
Authors: Seung-Won Oh, Alexis C. Wood, Seung-sik Hwang, Matthew Allison
Journal: JAMA Network Open (2022)

Evidence linking low-carbohydrate diets (LCDs) to mortality is limited among multiethnic populations.To evaluate the association between LCDs and mortality by race and ethnicity.The Multi-Ethnic Study of Atherosclerosis is a large, population-based prospective cohort study of adults aged 45 to 84 years recruited from 6 US communities. A total of 6109 participants without baseline cardiovascular disease were included in this analysis. Baseline data were collected from July 2000 to August 2002, with follow-up completed by December 2017. The data were analyzed between May 2021 and April 2022.Food frequency questionnaires were used to assess dietary intake. From these data, overall LCD scores were calculated from the percentages of energy intake from carbohydrates, fats, and proteins. Animal-based (emphasizing saturated fat and animal protein) and vegetable-based (emphasizing monounsaturated fat and vegetable protein) LCD scores were also calculated.All-cause and cause-specific mortality over a median follow-up of 15.9 years (IQR, 14.3-16.6 years).Among the 6109 participants (mean [SD] age, 62.3 [10.3] years; 3190 women [52.2%]; 1623 African American [26.6%], 701 Chinese American [11.5%], 1350 Hispanic [22.1%], and 2435 non-Hispanic White [39.8%]), there were 1391 deaths. Overall, LCD scores were not associated with mortality, but when analyses were stratified by race and ethnicity, a lower risk of all-cause and non-CV mortality was observed among Hispanic participants with moderate carbohydrate intake. Specifically, the hazard ratios for total mortality for overall LCD scores were 0.58 (95% CI, 0.40-0.84) for quintile 2, 0.67 (95% CI, 0.45-0.98) for quintile 3, 0.60 (95% CI, 0.41-0.87) for quintile 4, and 0.83 (95% CI, 0.57-1.21) for quintile 5, with quintile 1 as the reference group. A similar association was observed for animal-based (but not vegetable-based) LCD scores. In contrast, no significant associations were found between LCD scores and mortality risk in the other racial and ethnic groups.In this cohort study of multiethnic US adults, LCD score was not associated with mortality in the whole population. However, moderate carbohydrate intake was associated with a lower risk of mortality among Hispanic participants. These findings suggest that the association between carbohydrate intake and mortality may differ according to race and ethnicity. Dietary guidelines considering these differences may be necessary.
Dog ownership in infancy is protective for persistent wheeze in 17q21 asthma-risk carriers
Authors: Mauro Tutino, Raquel Granell, John A. Curtin, Sadia Haider, Sara Fontanella, Clare S. Murray, Graham Roberts, S. Hasan Arshad, Stephen Turner, Andrew P. Morris, Adnan Custovic, Angela Simpson
Journal: Journal of Allergy and Clinical Immunology (2022)

Asthma-associated single nucleotide polymorphisms from large genome-wide association studies only explain a fraction of genetic heritability. Likely causes of the missing heritability include broad phenotype definitions and gene-environment interactions (GxE). The mechanisms underlying GxE in asthma are poorly understood. Previous GxE studies on pet ownership showed discordant results.
A path to translation: How 3D patient tumor avatars enable next generation precision oncology
Authors: Shree Bose, Margarida Barroso, Milan G. Chheda, Hans Clevers, Elena Elez, Salma Kaochar, Scott E. Kopetz, Xiao-Nan Li, Funda Meric-Bernstam, Clifford A. Meyer, Haiwei Mou, Kristen M. Naegle, Martin F. Pera, Zinaida Perova, Katerina A. Politi, Benjamin J. Raphael, Paul Robson, Rosalie C. Sears, Josep Tabernero, David A. Tuveson, Alana L. Welm, Bryan E. Welm, Christopher D. Willey, Konstantin Salnikow, Jeffrey H. Chuang, Xiling Shen
Journal: Cancer Cell (2022)
HypoMap—a unified single-cell gene expression atlas of the murine hypothalamus
Authors: Lukas Steuernagel, Brian Y. H. Lam, Paul Klemm, Georgina K. C. Dowsett, Corinna A. Bauder, John A. Tadross, Tamara Sotelo Hitschfeld, Almudena del Rio Martin, Weiyi Chen, Alain J. de Solis, Henning Fenselau, Peter Davidsen, Irene Cimino, Sara N. Kohnke, Debra Rimmington, Anthony P. Coll, Andreas Beyer, Giles S. H. Yeo, Jens C. Brüning
Journal: Nature Metabolism (2022)
Ensuring remote diagnostics for pathologists: an open letter to the US Congress
Authors: Jochen K. Lennerz, Liron Pantanowitz, Mitual B. Amin, Isam-Eldin Eltoum, Meera R. Hameed, Alexana N. Kalof, Elham Khanafshar, Lakshmi P. Kunju, Audrey J. Lazenby, Kathleen T. Montone, Christopher N. Otis, Michelle D. Reid, Paul N. Staats, Christa L. Whitney-Miller, Catherine S. Abendroth, Manju Aron, George G. Birdsong, Ira J. Bleiweiss, Mary P. Bronner, Jennifer Chapman, Nicole A. Cipriani, Gustavo de la Roza, Michael J. Esposito, Oluwole Fadare, Karen Ferrer, Christopher D. Fletcher, David P. Frishberg, Fernando U. Garcia, Laurette Geldenhuys, Ryan M. Gill, Dorina Gui, Shams Halat, Omar Hameed, Jason L. Hornick, Aaron R. Huber, Dhanpat Jain, Nirag Jhala, Merce Jorda, Julie M. Jorns, Jeffrey Kaplan, Mahmoud A. Khalifa, Ashraf Khan, Grace E. Kim, Eun Y. Lee, Virginia A. LiVolsi, Teri Longacre, Cristina Magi-Galluzzi, Shannon J. McCall, Laron McPhaul, Vikas Mehta, Mihai Merzianu, Stacey B. Miller, Kyle H. Molberg, Andre L. Moreira, Bita V. Naini, Vania Nosé, Kathleen O’Toole, Maria Picken, Victor G. Prieto, James M. Pullman, Charles M. Quick, Jordan P. Reynolds, Andrew E. Rosenberg, Stuart J. Schnitt, Mary R. Schwartz, Marin Sekosan, Michael T. Smith, Aliyah Sohani, Anne Stowman, Vijay K. Vanguri, Beverly Wang, John C. Watts, Shi Wei, Kathleen Whitney, Mamoun Younes, Sui Zee, Erika R. Bracamonte
Journal: Nature Medicine (2022)
Rapalogs downmodulate intrinsic immunity and promote cell entry of SARS-CoV-2
Authors: Guoli Shi, Abhilash I Chiramel, Tiansheng Li, Kin Kui Lai, Adam D Kenney, Ashley Zani, Adrian C Eddy, Saliha Majdoul, Lizhi Zhang, Tirhas Dempsey, Paul A Beare, Swagata Kar, Jonathan W Yewdell, Sonja M Best, Jacob S Yount, Alex A Compton
Journal: Journal of Clinical Investigation (2022)

Severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) infection in immunocompromised individuals is associated with prolonged virus shedding and evolution of viral variants. Rapamycin and its analogs (rapalogs, including everolimus, temsirolimus, and ridaforolimus) are FDA approved as mTOR inhibitors for the treatment of human diseases, including cancer and autoimmunity. Rapalog use is commonly associated with an increased susceptibility to infection, which has been traditionally explained by impaired adaptive immunity. Here, we show that exposure to rapalogs increased susceptibility to SARS-CoV-2 infection in tissue culture and in immunologically naive rodents by antagonizing the cell-intrinsic immune response. We identified 1 rapalog (ridaforolimus) that was less potent in this regard and demonstrated that rapalogs promote spike-mediated entry into cells, by triggering the degradation of the antiviral proteins IFITM2 and IFITM3 via an endolysosomal remodeling program called microautophagy. Rapalogs that increased virus entry inhibited mTOR-mediated phosphorylation of the transcription factor TFEB, which facilitated its nuclear translocation and triggered microautophagy. In rodent models of infection, injection of rapamycin prior to and after virus exposure resulted in elevated SARS-CoV-2 replication and exacerbated viral disease, while ridaforolimus had milder effects. Overall, our findings indicate that preexisting use of certain rapalogs may elevate host susceptibility to SARS-CoV-2 infection and disease by activating lysosome-mediated suppression of intrinsic immunity.
Neurotensin neurons in the extended amygdala control dietary choice and energy homeostasis
Authors: Alessandro Furlan, Alberto Corona, Sara Boyle, Radhashree Sharma, Rachel Rubino, Jill Habel, Eva Carlotta Gablenz, Jacqueline Giovanniello, Semir Beyaz, Tobias Janowitz, Stephen David Shea, Bo Li
Journal: Nature Neuroscience (2022)
A multi-lab test of the facial feedback hypothesis by the Many Smiles Collaboration
Authors: Nicholas A. Coles, David S. March, Fernando Marmolejo-Ramos, Jeff T. Larsen, Nwadiogo C. Arinze, Izuchukwu L. G. Ndukaihe, Megan L. Willis, Francesco Foroni, Niv Reggev, Aviv Mokady, Patrick S. Forscher, John F. Hunter, Gwenaël Kaminski, Elif Yüvrük, Aycan Kapucu, Tamás Nagy, Nandor Hajdu, Julian Tejada, Raquel M. K. Freitag, Danilo Zambrano, Bidisha Som, Balazs Aczel, Krystian Barzykowski, Sylwia Adamus, Katarzyna Filip, Yuki Yamada, Ayumi Ikeda, Daniel L. Eaves, Carmel A. Levitan, Sydney Leiweke, Michal Parzuchowski, Natalie Butcher, Gerit Pfuhl, Dana M. Basnight-Brown, José A. Hinojosa, Pedro R. Montoro, Lady G. Javela D, Kevin Vezirian, Hans IJzerman, Natalia Trujillo, Sarah D. Pressman, Pascal M. Gygax, Asil A. Özdoğru, Susana Ruiz-Fernandez, Phoebe C. Ellsworth, Lowell Gaertner, Fritz Strack, Marco Marozzi, Marco Tullio Liuzza
Journal: Nature Human Behaviour (2022)
H3N8 subtype avian influenza virus originated from wild birds exhibited dual receptor-binding profiles
Authors: Jingman Tian, Minghui Li, Yulei Li, Xiaoli Bai, Xingdong Song, Zhiguo Zhao, Shenfeng Ge, Yuehui Li, Jianwen Liu, Jianzhong Shi, Xiaoliang Wang, Zhixin Li, Haining Zhou, Long Ma, Xianying Zeng, Guobin Tian, Yuntao Guan, Yanbing Li, Hualan Chen
Journal: Journal of Infection (2022)
Tocilizumab versus baricitinib in hospitalized patients with severe COVID-19: an open label, randomized controlled trial
Authors: Theodoros Karampitsakos, Ourania Papaioannou, Panagiota Tsiri, Matthaios Katsaras, Andreas Katsimpris, Andreas P. Kalogeropoulos, Elli Malakounidou, Eirini Zarkadi, Georgios Tsirikos, Vasiliki Georgiopoulou, Vasilina Sotiropoulou, Electra Koulousousa, Charikleia Chourpiliadi, Apostolos Matsioulas, Maria Lagadinou, Fotios Sampsonas, Karolina Akinosoglou, Markos Marangos, Argyris Tzouvelekis
Journal: Clinical Microbiology and Infection (2022)
Critical Illness Myopathy Alters Diaphragm Neuromuscular Junction Protein and Gene Expression
Authors: Ashley J. Smuder, Sanford Levine, Scott K. Powers
Journal: American Journal of Respiratory and Critical Care Medicine (2022)

"Critical Illness Myopathy Alters Diaphragm Neuromuscular Junction Protein and Gene Expression." American Journal of Respiratory and Critical Care Medicine, 207(3), pp. 358–361
Identification of exosomal biomarkers and its optimal isolation and detection method for the diagnosis of Parkinson's disease: A systematic review and meta-analysis
Authors: Irin Sultana Nila, Dewan Md. Sumsuzzman, Zeeshan Ahmad Khan, Jin Ho Jung, Ashura Suleiman Kazema, Sang Jin Kim, Yonggeun Hong
Journal: Ageing Research Reviews (2022)
Significance of hereditary gene alterations for the pathogenesis of adult bone marrow failure versus myeloid neoplasia
Authors: Yasuo Kubota, Misam Zawit, Jibran Durrani, Wenyi Shen, Waled Bahaj, Tariq Kewan, Ben Ponvilawan, Minako Mori, Manja Meggendorfer, Carmelo Gurnari, Thomas LaFramboise, Simone Feurstein, Mikkael A. Sekeres, Valeria Visconte, Lucy A. Godley, Torsten Haferlach, Jaroslaw P. Maciejewski
Journal: Leukemia (2022)
Social connectedness and cognitive decline
Authors: Adam R Roth
Journal: The Lancet Healthy Longevity (2022)

Cognitive impairment is a growing public health concern that affects millions of people worldwide. Alzheimer's disease and related dementia, which represent a leading cause of cognitive decline among older adults, has a high financial burden. Approximately US$1·3 trillion is spent on Alzheimer's disease and related dementia every year worldwide.1 Although there are more than 100 clinical trials of pharmaceutical agents for Alzheimer's disease and related dementia, no effective treatment exists.2 In response to the absence of effective pharmaceutical treatment, researchers are investigating non-pharmaceutical pathways leading to cognitive decline in later life.
Associations between social connections and cognition: a global collaborative individual participant data meta-analysis
Authors: Suraj Samtani, Gowsaly Mahalingam, Ben Chun Pan Lam, Darren M Lipnicki, Maria Fernanda Lima-Costa, Sergio Luís Blay, Erico Castro-Costa, Xiao Shifu, Maëlenn Guerchet, Pierre-Marie Preux, Antoine Gbessemehlan, Ingmar Skoog, Jenna Najar, Therese Rydberg Sterner, Nikolaos Scarmeas, Ki-Woong Kim, Steffi Riedel-Heller, Susanne Röhr, Alexander Pabst, Suzana Shahar, Katya Numbers, Mary Ganguli, Erin Jacobsen, Tiffany F Hughes, Michael Crowe, Tze Pin Ng, Jane Maddock, Anna Marseglia, René Mélis, Dorota Szcześniak, Henrik Wiegelmann, Myrra Vernooij-Dassen, Yun-Hee Jeon, Perminder S Sachdev, Henry Brodaty
Journal: The Lancet Healthy Longevity (2022)

Poor social connections (eg, small networks, infrequent interactions, and loneliness) are modifiable risk factors for cognitive decline. Existing meta-analyses are limited by reporting aggregate responses, a focus on global cognition, and combining social measures into single constructs. We aimed to investigate the association between social connection markers and the rate of annual change in cognition (ie, global and domain-specific), as well as sex differences, using an individual participant data meta-analysis.
Sexual Violence—Another Public Health Emergency
Authors: Kamila A. Alexander, Elizabeth Miller
Journal: JAMA Network Open (2022)

Emily L. Vogt, BA; Charley Jiang, MS; Quinton Jenkins, MPH; Maya J. Millette, BS; Martina T. Caldwell, MD, MS; Kathleen S. Mehari, MD; Erica E. Marsh, MD, MSCI
The Macrophage-Associated LncRNA <i>MALR</i> Facilitates ILF3 Liquid–Liquid Phase Separation to Promote HIF1α Signaling in Esophageal Cancer
Authors: Jia Liu, Ze-Xian Liu, Jia-Jun Li, Zhao-Lei Zeng, Jin-Hong Wang, Xiao-Jing Luo, Chau-Wei Wong, Jia-Bo Zheng, Heng-Ying Pu, Hai-Yu Mo, Hui Sheng, Qi-Nian Wu, Hao Li, Gang Wan, Bo Li, De-shen Wang, Rui-Hua Xu, Huai-Qiang Ju
Journal: Cancer Research (2022)

Abstract Tumor-associated macrophages (TAM) are among the most abundant immune cells in the tumor microenvironment and are important mediators of tumor development and progression. Here, we identified a macrophage-associated long noncoding RNA (lncRNA), MALR, that facilitates progression of esophageal squamous cell carcinoma (ESCC). TAM-mediated secretion of TNFα drove MALR upregulation in ESCC cells. MALR promoted aerobic glycolytic activity and facilitated angiogenesis by activating the HIF1α signaling pathway. Mechanistically, MALR bound the dsRBD1 domain of interleukin enhancer-binding factor 3 (ILF3), promoting ILF3 protein stability and ILF3-mediated liquid–liquid phase separation (LLPS), thereby enhancing HIF1α mRNA stability by preventing PARN-mediated degradation. Loss of MALR suppressed cell line–based and patient-derived xenograft tumor growth. Clinically, high expression of MALR positively correlated with HIF1α target gene expression and indicated poor prognoses for patients with esophageal cancer. Overall, this study uncovers the physiologic roles of MALR/ILF3-mediated LLPS in tumor microenvironment remodeling, highlighting the MALR–ILF3–HIF1α axis as a potential target for cancer therapy. Significance: Secretion of TNFα by tumor-associated macrophages stimulates cancer cells to upregulate lncRNA MALR, which induces ILF3 liquid–liquid phase separation and activation of HIF1α signaling to promote cancer progression.
Shared Cancer Dataset Analysis Identifies and Predicts the Quantitative Effects of Pan-Cancer Somatic Driver Variants
Authors: Jakob Landau, Linoy Tsaban, Adar Yaacov, Gil Ben Cohen, Shai Rosenberg
Journal: Cancer Research (2022)

Abstract Driver mutations endow tumors with selective advantages and produce an array of pathogenic effects. Determining the function of somatic variants is important for understanding cancer biology and identifying optimal therapies. Here, we compiled a shared dataset from several cancer genomic databases. Two measures were applied to 535 cancer genes based on observed and expected frequencies of driver variants as derived from cancer-specific rates of somatic mutagenesis. The first measure comprised a binary classifier based on a binomial test; the second was tumor variant amplitude (TVA), a continuous measure representing the selective advantage of individual variants. TVA outperformed all other computational tools in terms of its correlation with experimentally derived functional scores of cancer mutations. TVA also highly correlated with drug response, overall survival, and other clinical implications in relevant cancer genes. This study demonstrates how a selective advantage measure based on a large cancer dataset significantly impacts our understanding of the spectral effect of driver variants in cancer. The impact of this information will increase as cancer treatment becomes more precise and personalized to tumor-specific mutations. Significance: A new selective advantage estimation assists in oncogenic driver identification and relative effect measurements, enabling better prognostication, therapy selection, and prioritization.
Performance of 3 Sets of Criteria for Potentially Inappropriate Prescribing in Older People to Identify Inadequate Drug Treatment
Authors: Susanna M. Wallerstedt, Staffan A. Svensson, Johan Lönnbro, Fredrik Hieronymus, Johan Fastbom, Mikael Hoffmann, Naldy Parodi López
Journal: JAMA Network Open (2022)

Potentially inappropriate medications (PIMs) and potential prescribing omissions (PPOs) are used in research to reflect the quality of drug treatment in older people and have been suggested for inclusion in core outcome sets for evaluation of interventions for improved prescribing. Their validation so far, however, is primarily restricted to expert opinion-based processes.To evaluate the performance of 3 explicit PIM/PPO criteria sets as diagnostic tools to identify inadequate drug treatment in older patients.This diagnostic study analyzed patients aged 65 years or older consecutively included from 2 primary health care centers from October to November 2017. Data were analyzed from February to August 2022.The PIMs/PPOs were concordantly identified by 2 specialist physicians (2018-2019) retrospectively after a planned physician visit, using 3 European PIM/PPO criteria sets and without knowledge of this diagnostic study.Area under the receiver operating characteristic (ROC) curve, reflecting the ability of PIM/PPO criteria sets to identify the reference standard of inadequate drug treatment, determined by 2 specialist physicians in consensus. Inadequate drug treatment implied that additional action related to the medication could be medically justified before the next regular visit.A total of 302 patients were analyzed (median age, 74 [IQR, 69-81] years; 178 women [59%]; median number of drugs in the medication list, 6 [IQR, 3-9]); 98 patients (32%) had inadequate drug treatment. A total of 0 to 8 PIMs/PPOs per patient were identified using the Screening Tool of Older Persons' Prescriptions (STOPP)/Screening Tool to Alert to Right Treatment (START) criteria, 0 to 6 with the European EU(7)-PIM list, and 0 to 12 with the Swedish set of indicators of prescribing quality. The areas under the ROC curve for the 3 sets to identify the reference standard for inadequate drug treatment were 0.60 (95% CI, 0.53-0.66) for the STOPP/START criteria, 0.69 (95% CI, 0.63-0.75) for the EU(7)-PIM list, and 0.73 (95% CI, 0.67-0.80) for the Swedish set. For comparison, the area under the ROC curve was 0.71 (95% CI, 0.65-0.78) using the number of drugs in the medication list.In this diagnostic study, the evaluated PIM/PPO sets had poor to fair performance as diagnostic tools to identify inadequate drug treatment, comparable with a simple count of the number of drugs in the medication list. These findings suggest that use of PIMs/PPOs as indicators of drug treatment quality in core outcome sets for the evaluation of interventions for improved prescribing may need reconsideration.
Association Between Pretransplant Dialysis Modality and Kidney Transplant Outcomes
Authors: Tanun Ngamvichchukorn, Chidchanok Ruengorn, Kajohnsak Noppakun, Kednapa Thavorn, Brian Hutton, Manish M. Sood, Greg A. Knoll, Surapon Nochaiwong
Journal: JAMA Network Open (2022)

Importance The benefits and disadvantages of different pretransplant dialysis modalities and their posttransplant outcomes remain unclear in contemporary kidney transplant care. Objective To summarize the available evidence of the association of different pretransplant dialysis modalities, including hemodialysis and peritoneal dialysis (PD), with posttransplant outcomes. Data Sources MEDLINE, Embase, PubMed, Cochrane Library, Scopus, CINAHL, and gray literature were searched from inception to March 18, 2022 (updated to April 1, 2022), for relevant studies and with no language restrictions. Study Selection Randomized clinical trials and nonrandomized observational (case-control and cohort) studies that investigated the association between pretransplant dialysis modality and posttransplant outcomes regardless of age or donor sources (living or deceased) were abstracted independently by 2 reviewers. Data Extraction and Synthesis Following Preferred Reporting Items for Systematic Reviews and Meta-analyses and Meta-analysis of Observational Studies in Epidemiology reporting guidelines, 2 reviewers independently extracted relevant information using a standardized approach. Random-effects meta-analysis was used to estimate pooled adjusted hazard ratio (HR) or odds ratio and 95% CI. Main Outcomes and Measures Primary outcomes included all-cause mortality, overall graft failure, death-censored graft failure, and delayed graft function. Secondary outcomes included acute rejection, graft vessel thrombosis, oliguria, de novo heart failure, and new-onset diabetes after transplant. Results The study analyzed 26 nonrandomized studies (1 case-control and 25 cohort), including 269 715 patients (mean recipient age range, 14.5-67.0 years; reported proportions of female individuals, 29.4%-66.9%) whose outcomes associated with pretransplant hemodialysis vs pretransplant PD were compared. No significant difference, with very low certainty of evidence, was observed between pretransplant PD and all-cause mortality (13 studies; n = 221 815; HR, 0.92 [95% CI, 0.84-1.01]; P = .08) as well as death-censored graft failure (5 studies; n = 96 439; HR, 0.98 [95% CI, 0.85-1.14]; P = .81). However, pretransplant PD was associated with a lower risk for overall graft failure (10 studies; n = 209 287; HR, 0.96 [95% CI, 0.92-0.99]; P = .02; very low certainty of evidence) and delayed graft function (6 studies; n = 47 118; odds ratio, 0.73 [95% CI, 0.70-0.76]; P &amp;amp;lt; .001; low certainty of evidence). Secondary outcomes were inconclusive due to few studies with available data. Conclusions and Relevance Results of the study suggest that pretransplant PD is a preferred dialysis modality option during the transition to kidney transplant. Future studies are warranted to address shared decision-making between health care professionals, patients, and caregivers as well as patient preferences.